Weekly Therapy Matches TB Care Standard

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

In a 6-month, randomized regimen, once-a-week high-dose rifapentine plus moxiﬂoxacin in the continuation phase was non-inferior to control in patients with new smear-positive pulmonary tuberculosis; it was also safe and well tolerated.

ATLANTA – A novel TB treatment regimen featuring once-a-week therapy produced results equivalent to those seen with the standard once-daily approach, a researcher said here.

The finding, from a randomized trial, could have a "massive impact on adherence rates and cure rates," said Amina Jindani, MD, of England's St. George's University of London.

The novel regimen would allow more intensive supervision of therapy in the so-called continuation phase of the 6-month TB treatment, Jindani reported here at the Conference on Retroviruses and Opportunistic Infections.

The findings have "rekindled" hope for once-weekly TB therapy, commented Richard Chaisson, MD, of Johns Hopkins University, who moderated a press conference at which the study was presented.

Chaisson noted that a U.S. trial, conducted a decade ago, did not show as good a result and -- although the FDA approved weekly treatment with rifapentine (Priftin) – many clinicians were not convinced.

"I think everyone had given up hope for a once-weekly regimen," he told MedPage Today. "The hope has been rekindled."

The current World Health Organization recommendations for TB treatment involve daily isoniazid (Nydrazid), rifampin (Rifadin), pyrazinamide, and ethambutol (Myambutol) for 2 months, followed by daily isoniazid and rifampin for another 4 months.

During the early intensive phase, patients take their drugs under supervision – so-called directly observed therapy – but many falter in adherence during the continuation phase, when they take the medications without supervision.

In the novel regimen, treatment was still daily and directly observed in the intensive phase, but the antibiotic moxifloxacin (Avelox) was substituted for isoniazid.

The big difference, Jindani said, came in the continuation phase, when 1,200 milligrams of rifapentine and moxifloxacin, taken weekly, were substituted for daily isoniazid and rifampin.

The weekly dosing, she said, allowed directly observed therapy to be continued throughout the 6 months of treatment.

In the study, Jindani and colleagues looked to see if the two regimens were within a 6-percentage point non-inferiority margin in terms of treatment failures 18 months after randomization.

In the intent-to treat analysis, she reported, the proportions of failures were identical – 14% in each arm – and therefore the difference was within the non-inferiority margin.

A shorter, 4-month regimen based on rifapentine and moxifloxacin was inferior to the standard treatment, she reported.

The adverse event rates were also similar between the two successful regimens. There were 17 severe or life-threatening events – grades 3 and 4 – in each arm at any time during chemotherapy, Jindani reported.

Jindani said earlier trials of rifapentine had unacceptably high relapse rates, which she and her colleagues attempted to overcome by giving a higher dose of the drug.

But Chaisson and other experts said changing clinical practice is going to take time because most TB therapy is conducted under strict guidelines by public health authorities, even in the U.S.

Among other things, a change would require retraining thousands of nurses in the new protocol, commented Andreas Diacon, PhD, of Stellenbosch University in Tygerberg, South Africa, who was not part of the study.

And, he told MedPage Today, public health authorities will probably want to have cost-effectiveness data before they make any changes.

Jindani herself – a renowned TB researcher – said the only obstacle she sees is cost, because rifapentine, is much more expensive than rifampin. On the other hand, she told MedPage Today, "if there's uptake, the cost will very, very quickly come down."

She added there are some people – those resistant to isoniazid, for instance -- for whom the new regimen could be used immediately.

The study had support from the European & Developing Countries Clinical Trials Partnership, the Wellcome Trust, sanofi-aventis, Genus Pharmaceuticals, and Sandoz SA. Jindani did not make any financial disclosures.

Chaisson reported financial links with Merck and Vertex.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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